Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  7
• Reference
  J:122161 Blackburn AC, et al., Genetic mapping in mice identifies DMBT1 as a candidate modifier of mammary tumors and breast cancer risk. Am J Pathol. 2007 Jun;170(6):2030-41
• ID
  MGI:3715516

Genes

Gene	Assay Type
Suprmam1	resistance/susceptibility
Hbb-b2	reported elsewhere
Spon1	reported elsewhere
Trim12a	reported elsewhere
Thumpd1	reported elsewhere
Dmbt1	reported elsewhere

Notes

• Experiment
  Linkage analysis was performed on 224 female (C57BL/6J x BALB/cMed-Trp53^tm1Tyj)F1 x BALB/cMed-Trp53^tm1Tyj backcross animals to identify genetic modifiers of mammary tumor susceptibility. Female animals were monitored weekly for tumor development and morbidity for 18 months. Genome scan was performed by genotyping 150 single nucleotide polymorphisms (SNPs) in pooled DNA from tumor-bearing (n=85) and non-tumor-bearing (n=91) mice.
  
  A locus on mouse Chromosome 7 showed significant linkage to mammary tumor development in Trp53^tm1Tyj heterozygous animals with LOD=3.5 near SNP marker M64879_201_1. This QTL spans 107.9 Mb - 120.5 Mb and is named Suprmam1 (suppressor of mammary tumors 1). There are potentially 2 QTLs within this interval. Homozygosity for BALB/cMed-derived alleles at Suprmam1 in conjunction with one Trp53^tm1Tyj allele confers increased incidence of mammary tumors, decreased tumor latency by 10 weeks (61.1 weeks vs 70.7 weeks), and decreased mammary tumor-free survival.
  
  Microarray analysis was performed on mammary tissue RNA from C57BL/6J-Trp53^tm1Tyj and BALB/cMed-Trp53^tm1Tyj animals to identify candidate genes for Suprmam1. Hbb-b2 (50 cM) and Spon1 expression is increased in BALB/cMed-Trp53^tm1Tyj compared to C57BL/6J-Trp53^tm1Tyj while Trim12, Thumpd1 (59 cM), and Dmbt1 expression is decreased in BALB/cMed-Trp53^tm1Tyj. Dbmt1 is of particular interest because it has been previously described as a putative tumor suppressor gene. Dmbt1 expression is expressed >5-fold specifically in the mammary glands of C57BL/6J-Trp53^tm1Tyj compared to BALB/cMed-Trp53^tm1Tyj. Decreased DMBT1 expression is also associated with breast cancer susceptibility in human females.